P1007: PHASE 2, OPEN-LABEL, MULTICENTER, SINGLE-ARM STUDY INVESTIGATING THE EFFICACY AND SAFETY OF ROPEGINTERFERON ALFA-2B IN JAPANESE PATIENTS WITH POLYCYTHEMIA VERA
Authors: K. Kirito, Y. Edahiro, K. Ohishi, A. Gotoh, K. Takenaka, H. Shibayama, T. Shimizu, K. Usuki, K. Shimoda, M. Ito, S. A. VanWart, O. Zagrijtschuk, A. Qin, H. Kawase, N. Miyachi, T. Sato, N. Komatsu
Journal: HemaSphere (2022)

Background: Polycythemia vera (PV) is a BCR–ABL-negative myeloproliferative neoplasms with a JAK2 gene mutation, that can be complicated by thrombosis and hemorrhage. It may also evolve to secondary acute myeloid leukemia, which has a poor prognosis and is potentially fatal. Ropeginterferon alfa-2b, a peg-proline-interferon alfa-2b with improved pharmacokinetic properties, allowing for less frequent administration and better tolerability, has been shown in clinical studies (PEGINVERA, PROUD-PV, CONTINUATION-PV) to be efficacious and have a favorable safety profile. However, its efficacy and safety have not been evaluated in Japanese PV patients. Aims: The aim of this phase 2, single-arm study (NCT04182100) was to investigate the efficacy and safety of ropeginterferon alfa-2b in Japanese patients with PV to assess the clinical utility of this cytoreductive therapy as a treatment option. Methods: Japanese patients aged ≥20 years with a PV diagnosis according to World Health Organization 2008/2016 criteria and who were unsuitable candidates for current standard treatment were included, and patients being refractory to hydroxyurea (HU), symptomatic splenomegaly, or previous treatment with interferon alfa were excluded. Ropeginterferon alfa-2b was administered subcutaneously every 2 weeks for 12 months (M) at a starting dose of 100μg (50μg in patients receiving HU). This was increased by 50μg every 2 weeks until patients had achieved complete hematological response (CHR): hematocrit <45% without phlebotomy in the preceding 3M, platelets ≤400×109/L, leukocytes ≤10×109 /L, or reached the maximum recommended single dose (500μg). The primary endpoint was phlebotomy-free CHR at 9M and 12M (end of treatment [EOT]). Secondary endpoints were change in hematologic parameters, CHR in patients with or without prior HU use, JAK2V617F allele burden, molecular response, and frequency of phlebotomy. Safety endpoints were incidence of treatment-emergent adverse events (TEAEs) and AEs of special interest. Results: A total of 29 patients comprised the intent-to-treat population (median age, 54 years; mean hematocrit, 46.85%; mean platelets, 747.3×109/L; mean leukocytes, 17.07×109/L at baseline). Twenty-seven patients had a JAK2V617F mutation (mean allele burden, 72.19%). Two patients discontinued the study (one withdrew consent, the other due to an AE [silent thyroiditis]). The primary outcome of durable CHR without phlebotomy at 9M and EOT was achieved by 8/29 (27.6%) patients. Hematocrit, platelets, and leukocytes decreased over time (mean±SD change from baseline to EOT: –5.45±6.66%, –493.6±374.9×109/L, –11.71±8.38×109/L, respectively), and all parameters improved to their target value range. The proportion of patients with CHR at EOT was similar in patients with or without prior HU use (Table). JAK2V617F allele burden decreased over time (change from baseline to EOT: mean ±SD, –19.17±22.64; Median [min, max], -11.62 [-74.80,33.80]; n=26). Molecular response increased over time. Eight (27.6%) patients did not require phlebotomy. TEAEs occurred in all patients; however, no event of grade ≥ 3 occurred. The most common TEAEs were alopecia (55.2%), fatigue (27.6%) and influenza-like illness (27.6%). AEs of special interest, which could be both disease and treatment-related, occurred in 9 (31.0%) of the patients and were related to the study treatment in 5 (17.2%) of the patients. Image:Summary/Conclusion: Ropeginterferon alfa-2b is a safe and efficacious treatment option in Japanese patients with polycythemia vera.